PUBLICATION
An automated screening method for detecting compounds with goitrogenic activity using transgenic zebrafish embryos
- Authors
- Jarque, S., Fetter, E., Veneman, W.J., Spaink, H.P., Peravali, R., Strähle, U., Scholz, S.
- ID
- ZDB-PUB-180830-10
- Date
- 2018
- Source
- PLoS One 13: e0203087 (Journal)
- Registered Authors
- Peravali, Ravindra, Spaink, Herman P., Strähle, Uwe
- Keywords
- none
- MeSH Terms
-
- Thyroid Gland/drug effects
- Thyroid Gland/metabolism
- Animals, Genetically Modified
- Dose-Response Relationship, Drug
- Animals
- Luminescent Proteins/genetics
- Luminescent Proteins/metabolism
- Image Processing, Computer-Assisted
- Automation, Laboratory*
- Microscopy, Fluorescence
- Embryo, Nonmammalian/drug effects
- Embryo, Nonmammalian/metabolism
- Antithyroid Agents/pharmacology*
- Hydrophobic and Hydrophilic Interactions
- Zebrafish
- Drug Evaluation, Preclinical/methods*
- PubMed
- 30157258 Full text @ PLoS One
- CTD
- 30157258
Citation
Jarque, S., Fetter, E., Veneman, W.J., Spaink, H.P., Peravali, R., Strähle, U., Scholz, S. (2018) An automated screening method for detecting compounds with goitrogenic activity using transgenic zebrafish embryos. PLoS One. 13:e0203087.
Abstract
The knowledge on environmentally relevant chemicals that may interfere with thyroid signaling is scarce. Here, we present a method for the screening of goitrogens, compounds that disrupt the thyroid gland function, based on the automatic orientation of zebrafish in a glass capillary and a subsequent imaging of reporter gene fluorescence in the thyroid gland of embryos of the transgenic zebrafish line tg(tg:mCherry). The tg(tg:mCherry) reporter gene indicates a compensatory upregulation of thyroglobulin, the thyroid hormone precursor, in response to inhibition of thyroid hormone synthesis. Fish embryos were exposed to a negative control compound (3,4-dichloroaniline), or a concentration series of known goitrogenic compounds (resorcinol, methimazole, potassium perchlorate, 6-propyl-2-thiouracil, ethylenethiourea, phloroglucinol, pyrazole) with maximum exposure concentration selected based on mortality and/or solubility. Exposure to 3,4-dichloroaniline decreased the fluorescence signal. All goitrogenic compounds exhibited clear concentration-dependent inductions of reporter fluorescence 1.4 to 2.6 fold above control levels. Concentration-response modelling was used to calculate goitrogenic potencies based on EC50 values. The new automated method offers an efficient screening approach for goitrogenic activity.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping